The Salk Institute for Biological Studies

University of California

The United States Government as Represented by the Department of Veterans Affairs

David R Schubert

Pamela A Maher

Yuanbin Liu

Thomas J Baiga

Wolfgang H Fischer

Gregory M Cole

Sally A Frautschy

Chandramouli Chiruta

The present invention provides neuroprotective polyphenol compounds, which can be synthetic analogs of fisetin, baicalein or chlorogenic acid, that maintain neuroprotective, anti-inflammatory, glutathione promoting, and/or antioxidant properties. The neuroprotective polyphenol compounds are useful for promoting, enhancing and/or increasing neuron protection, growth and/or regeneration. The polyphenol compounds further find use for increasing and or maintaining intracellular glutathione (GSH) levels. The polyphenol compounds are also useful for treating, preventing, mitigating and/or delaying neurodegenerative conditions, including diabetes, Parkinson's disease, Huntington's disease, Alzheimer's disease, non-Alzheimer's dementias, multiple sclerosis, traumatic brain injury, spinal cord injury or ALS.

Neuroprotective polyphenol analogs

Nutraceutical formulations that improve cognitive function in adults diagnosed with neurodegenerative disease are provided, which comprise a combination of fisetin and DHA.

Medical food for cognitive decline

In accordance with the present invention, there are provided novel compounds that have a variety of properties, i.e., antioxidant, anti-inflammatory, antiviral, antibacterial, and antifungal properties. Invention compounds, therefore, have the ability to impart a variety of beneficial physiological effects, e.g., to protect neurons and/or to promote neuroregeneration and/or to promote memory formation and/or to act as protein phosphatase or kinase inhibitors and/or to act as lipoxygenase inhibitors. Such compounds are useful for treatment of a variety of indications, including neurodegenerative diseases and conditions, diabetes, ischemia associated with heart disease, and memory deficit. In another aspect of the present invention, there are also provided formulations containing one or more of the above-described compounds, optionally further containing additional neurologically active compound(s) and/or adjuvants to facilitate delivery thereof across the blood/brain barrier. In still another aspect of the present invention, there are further provided methods for treating a wide variety of neurological indications, e.g., acute neural injuries, chronic injuries, promoting memory formation, and the like.

Methods for treating a variety of diseases and conditions, and compounds useful therefor

Disclosed herein, inter alia, are methods and compositions for treating a complication of diabetes or a vascular disease using a 5-desoxy-flavone and/or 5-desoxy-flavonol.

Methods and compositions for treating complications of diabetes and vascular diseases using flavones

In accordance with the present invention, there are provided novel compounds that protect neurons and/or promote neuroregeneration and/or promote memory formation. Such compounds are useful for treatment of a variety of neural disorders and conditions. In another aspect of the present invention, there are also provided formulations containing one or more of the above-described compounds, optionally further containing additional neurologically active compound(s) and/or adjuvants to facilitate delivery thereof across the blood/brain barrier. In still another aspect of the present invention, there are further provided methods for treating a wide variety of neurological indications, e.g., acute neural injuries, chronic injuries, promoting memory formation, and the like.

Methods for treating neural disorders and conditions, and compounds useful therefor

In accordance with the present invention, there are provided novel methods of blocking amyloid protein toxicity in cells using polycylic compounds. Also provided are novel methods of decreasing amyloid protein production in cells and methods of inhibiting cell death. Invention methods can be used to prevent and treat a diverse class of disease conditions, known as amyloidoses, which are all related to the occurrence of amyloid protein deposits. Invention methods further provide methods of identifying compounds that can block amyloid toxicity or block the amyloid protein induced inhibition of MMT reduction.

Methods for protecting cells from amyloid toxicity and for inhibiting amyloid protein production

Neurotrophic growth factor proteins isolated from novel clonal cell lines grown in culture are mitogenic for fibroblasts and glial cells; some promote nerve cell survival and are prospectively useful in treating diseases such as Parkinson's and Alzheimer's which result in cell death in the nervous system, as well as in treating patients prone to epileptic seizures and patients suffering from trauma to the CNS. Certain of these proteins may be useful in nerve regeneration as well as in treating such diseases and injuries. Some are particularly useful in promoting lung development. These proteins are also useful in methods of treating a patient to promote nerve cell regeneration in degenerative eye diseases. The proteins can be topically applied in suitable compositions for wound-healing applications, and they can be administered parenterally to promote lung development and to treat patients afflicted with nerve damage and/or nerve disease.

DNA encoding neurotrophic growth factors

Proteins isolated from novel clonal cell lines grown in culture are mitogenic for fibroblasts, and glial cells; some promote nerve cell survival and are prospectively useful in treating diseases such as Parkinson's and Alzheimer's which result in cell death in the nervous system, as well as in treating patients prone to epileptic seizures and patients suffering from trauma to the CNS. Certain of these proteins may be useful in nerve regeneration as well as in treating such diseases and injuries. Some are particularly useful in promoting lung development. The proteins can be topically applied in suitable compositions for wound-healing applications, and they can be administered parenterally to promote lung development and to treat patients afflicted with nerve damage and/or nerve disease.

Growing community of inventors

La Jolla, CA, United States of America

David R Schubert